Studies involve development of approaches for the use of semisynthesis in the investigation of interacting peptide-protein complexes. To this end, polypeptides and protein fragments have been prepared which interact with complementary native proteins or protein fragments to form biologically active complexes. Methods have been developed for purification of semisynthetic peptide-protein derivatives in a state suitable for detailed conformational and functional characterization. By this methodology, studies are being made on the influence of side-chain characteristics on peptide-protein interaction, conformation, stability, and function. A model system used extensively in these studies is bovine pancreatic ribonuclease-S', an enzymically active complex of protein fragments ribonuclease-S-(1-20) and ribonuclease-S-(21-124). Semisynthetic analogues of the native complex are obtained by chemical synthesis (solid-phase procedure) of ribonuclease-S-(1-20) variants. With the latter, the microenvironments of loci, specifically chosen based on the X-ray crystallographic model of ribonuclease-S are studied, using spectroscopic, (C13 and proton NMR absorption) enzymic, affinity chromatographic, and other methods. Also experiments have been initiated on the interaction of bovine neurophysin-II with C13-enriched synthetic oxytocin which have allowed implications to be made on the mode of interaction of the neurohypophyseal hormone with its carrier protein.